Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin (SRIF) and GRFs play key roles in regulating GH secretion. We previously presented a model of SRIF-cAMP interaction; SRIF blocks rat (r) GH release without preventing its accumulation in a potentially releasable pool. This phenomenon may represent a mechanism whereby tonic SRIF inhibition and its subsequent reduction or withdrawal can modulate the magnitude if not the initiation of rGH pulses. Herein we test that model using human GRF-44 (hGRF-44). Tritium-prelabeled rat anterior pituitary fragments were perifused until stored [3H]rGH and [3H]rPRL release rates were stable. SRIF (10 or 25 nM), with and without hGRF-44 (3 or 10 nM), was added in short (1-h hGRF-44) and long (3-h hGRF-44) protocols; SRIF was then withdrawn while hGRF-44 was continued. Release of stored prelabeled [3H]rGH and [3H]rPRL was assessed by immunoprecipitation. Effects on PRL release were followed for comparison. SRIF-induced inhibition of release was only partially reversed by hGRF-44. At these concentrations and so long as SRIF was present, hGRF-44 could not stimulate the rate of hormone release to values above pre-SRIF basal rates. On the other hand, the amplitude of post-SRIF rebound release was increased by prolonging exposure to SRIF alone, by including hGRF-44 with SRIF, by increasing the amount of hGRF-44 included with SRIF, by prolonging exposure to hGRF-44 plus SRIF, and by using a smaller concentration of SRIF during exposure to hGRF-44. Interaction of hGRF-44-SRIF effects generated peak rates of hormone release after SRIF withdrawal which exceeded the maximum rates achieved using hGRF-44 alone in this system. Lactotroph responses were much smaller, but qualitatively resembled somatotroph responses. We conclude that the interplay of simultaneous hGRF-44 and SRIF effects can regulate the amplitude of rGH pulses. Although GRF can initiate physiological GH release, and GRF antisera can block GH pulses, we suggest that the surge of release that follows reduction of SRIF-induced inhibitory tone in vitro represents a potential mechanism that could contribute to the initiation of some pulses of release. Finally, we also present a theoretical model of secretagogue interactions at the cellular level to explain our results. The model is compatible with either a homogeneous cell population in which each secretory cell has multiple capabilities or a heterogeneous cell population composed of cell subgroups with complementary secretory abilities.
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PMID:Combined effects of human growth hormone (GH)-releasing factor-44 (GRF) and somatostatin (SRIF) on post-SRIF rebound release of GH and prolactin: a model for GRF-SRIF modulation of secretion. 290 Jan 35

Ten acromegalics received daily doses of 200-300 micrograms of a long-acting somatostatin analog, SMS 201-995 (Sandostatin, SMS), for an average of 64 weeks. Basal mean GH values of 44 +/- (SE) 7.8 ng/ml had fallen into the normal range at the end of the observation period (mean 64 weeks). This effect was accompanied by a substantial drop in somatomedin-C values. Reduction of pituitary tumor size could be documented in 3 of 6 patients. Whereas SMS did not affect high plasma PRL in 4 microprolactinoma patients, lactotrophs turned sensitive to this agent in mixed GH/PRL tumors. In a comparative study between SMS and bromocriptine, the former normalized circulating GH in 10 of 17 acromegalics in an acute trial, whereas bromocriptine was effective in only 5. A combination of both substances was effective in 2 of 3 patients who were insensitive to single drug administration. Cultures of GH-secreting tumor cells showed a statistically significant hormone decrease in the medium when exposed to SMS. However, in some instances, a diminution of the GH contents of the tumor cells was also observed, presumably as the basis for intracellular breakdown and clinical tumor shrinkage.
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PMID:Somatostatin analog treatment of acromegaly: new aspects. 290 Jan 90

Recently, we have developed a long-acting delivery system for our somatostatin (SS) analog RC-160 based on injectable microcapsules in poly-(D,L-lactide-coglycolide). We studied the capacity of this formulation to repeatedly block the GH secretion induced by administration of GRF-(1-29)NH2 (GRF) on different days. Male rats anesthetized with pentobarbital were injected iv with 2.5 micrograms/kg BW GRF-(1-29)NH2 or saline. Five minutes later, blood samples were taken for GH measurement, and the animals were injected im with RC-160 microcapsules at a dose calculated to release 25 micrograms/day of the analog for 7 days or with the vehicle. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules. GRF administration increased GH levels at the four times tested (P less than 0.01) in the control group injected with vehicle, while RC-160 microcapsules inhibited the GH response for more than 96 h (P less than 0.01). The GH levels augmented by pentobarbital were also decreased by the RC-160 microcapsules (P less than 0.01). Animals treated with microcapsules showed smaller increases in their body weight than untreated rats (P less than 0.05). We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC-160 microcapsules. These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC-160 and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels.
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PMID:Delayed release formulation of the somatostatin analog RC-160 inhibits the growth hormone (GH) response to GH-releasing factor-(1-29)NH2 and decreases elevated prolactin levels in rats. 290 38

To determine how arginine (Arg) stimulates GH secretion, we investigated its interaction with GHRH in vivo and in vitro. Six normal men were studied on four occasions: 1) Arg-TRH, 30 g arginine were administered in 500 mL saline in 30 min, followed by an injection of 200 micrograms TRH; 2) GHRH-Arg-TRH, 100 micrograms GHRH-(1-44) were given iv as a bolus immediately before the Arg infusion, followed by 200 micrograms TRH, iv; 3) GHRH test, 100 micrograms GHRH were given as an iv bolus; and 4) TRH test, 200 micrograms TRH were given iv as a bolus dose. Blood samples were collected at 15-min intervals for 30 min before and 120 min after the start of each infusion. Anterior pituitary cells from rats were coincubated with Arg (3, 6, 15, 30, and 60 mg/mL) and GHRH (0.05, 1, 5, and 10 nmol/L) for a period of 3 h. Rat GH was measured in the medium. After Arg-TRH the mean serum GH concentration increased significantly from 0.6 to 23.3 +/- 7.3 (+/- SE) micrograms/L at 60 min. TRH increased serum TSH and PRL significantly (maximum TSH, 11.1 +/- 1.8 mU/L; maximum PRL, 74.6 +/- 8.4 micrograms/L). After GHRH-Arg-TRH, the maximal serum GH level was significantly higher (72.7 +/- 13.4 micrograms/L) than that after Arg-TRH alone, whereas serum TSH and PRL increased to comparable levels (TSH, 10.2 +/- 3.0 mU/L; PRL, 64.4 +/- 13.6 micrograms/L). GHRH alone increased serum GH to 44.9 +/- 9.8 micrograms/L, significantly less than when GHRH, Arg, and TRH were given. TRH alone increased serum TSH to 6.6 +/- 0.6 mU/L, significantly less than the TSH response to Arg-TRH. The PRL increase after TRH only also was lower (47.2 +/- 6.8 micrograms/L) than the PRL response after Arg-TRH. In vitro Arg had no effect on basal and GHRH-stimulated GH secretion. Our results indicate that Arg administered with GHRH led to higher serum GH levels than did a maximally stimulatory dose of GHRH or Arg alone. The serum TSH response to Arg-TRH also was greater than that to TRH alone. We conclude that the stimulatory effects of Arg are mediated by suppression of endogenous somatostatin secretion.
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PMID:Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. 290 66

To determine whether human calcitonin inhibits GH secretion in man, as has been described for salmon calcitonin, the effect of an i.v. bolus of human calcitonin or saline on GH release after either insulin-induced hypoglycaemia or the administration of GH-releasing hormone (GHRH) or saline was studied. After the injection of calcitonin, no spontaneous GH surges were seen; the GH response to hypoglycaemia was diminished and the response to GHRH almost completely suppressed. Administration of calcitonin also caused a small and transient rise in plasma PRL and TSH but not LH levels, and no change in the integrated PRL or TSH response. Calcium and magnesium levels did not change. It is concluded that human calcitonin suppresses GH secretion in man, but not by suppressing GHRH and probably not by increasing somatostatin release. In addition, calcitonin has limited PRL and TSH-releasing activity.
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PMID:The effect of calcitonin on growth hormone secretion in man. 290 3

An analysis of the GH release-inhibiting action of the opioid kappa receptor agonists bremazocine and U-50,488, established earlier, was attempted by testing the agonists against activation of GH secretion by morphine or clonidine in male rats bearing right atrial cannulae for serial blood sampling and drug delivery. Both kappa agonists inhibited the effect of subsequent administration of clonidine in a dose-related manner. Bremazocine was approximately ten times more potent than U-50,488, a ratio corresponding to the known affinities of the two compounds for the kappa receptors. The inhibiting action of bremazocine was more strongly reversed by the preferential kappa receptor antagonist Mr-2266 than by naloxone, neither of which interfered with the GH-stimulating effect of clonidine. Bremazocine, however, did not alter the activation of GH secretion by exogenous growth hormone releasing factor. Thus, the inhibiting effect of bremazocine and probably U-50,488 seems to be derived from stimulation of the kappa receptors which in turn activates a GH release inhibiting mechanism of unknown identify which, however, does not involve release of somatostatin. Both kappa agonists also inhibited the effect of morphine, but in this case U-50,488 was approximately hundred times less effective than bremazocine. Since bremazocine and U-50,488 are antagonists of the delta receptors, which seem to mediate the GH-releasing effect to morphine, their inhibiting effect in this instance may be related to this property rather than to an action on the kappa receptors. Bremazocine, but not U-50,488, was also highly effective in inhibiting stimulation of PRL secretion by morphine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Opioid kappa receptors and the secretion of prolactin (PRL) and growth hormone (GH) in the rat. II. GH and PRL release-inhibiting effects of the opioid kappa receptor agonists bremazocine and U-50,488. 300 66

Using combined autoradiographic and immunohistochemical techniques, specific somatostatin (SRIH) receptors were measured in 31 human pituitary tumors. SRIH receptor distribution was compared with that of immunoreactive GH and PRL in the same tissue sections. Among the 10 tumors from acromegalic patients, 7 contained a high or medium density of SRIH receptors, whereas only a low density of such receptors was present in the remaining 3 tumors despite a comparably high concentration of immunoreactive GH in all 10 tumors. No correlation between plasma GH levels and SRIH receptors was found. One corticotroph tumor was SRIH receptor negative. Among the 5 prolactinomas tested, only 1 contained a significant density of SRIH receptors, the distribution of which did not correlate with that of immunoreactive PRL cells. Interestingly, among the 15 endocrine-inactive adenomas investigated, 6 had a measurable, sometimes high, density of SRIH receptors despite undetectable GH, PRL, or TSH immunoreactivity. These results suggest that based on their SRIH receptor content, there may be subclasses of GH-producing pituitary adenomas. The difference in SRIH receptor density may be an explanation for the clinically described differential responsiveness of acromegalic patients to SRIH. The results also suggest that subclasses of endocrine-inactive pituitary adenomas may exist; some of them contain significant amounts of SRIH receptors, which may be responsive to SRIH treatment.
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PMID:Visualization of somatostatin receptors and correlation with immunoreactive growth hormone and prolactin in human pituitary adenomas: evidence for different tumor subclasses. 303 58

The hypothesis that insulin hypoglycemia-induced GH release is mediated by a decrease in hypothalamic somatostatin (SRIH) secretion was tested by investigating whether insulin administration enhanced the responses of SRIH-sensitive pituitary hormones to hypothalamic hormone stimulation. Eight normal men were given a combined iv injection of GHRH (1 microgram/kg) and TRH (0.3 microgram/kg) on two occasions, on one of which regular insulin (0.1 U/kg, iv) was given 30 min before GHRH-TRH administration. Insulin hypoglycemia augmented the maximal incremental (P less than 0.01) and integrated (P less than 0.025) plasma GH responses to GHRH. In contrast, plasma TSH responses to TRH were diminished by insulin (maximal increment, P less than 0.025; integrated response, P less than 0.05). TRH-stimulated PRL secretion was not altered by prior insulin administration. The enhancement of GH responsiveness to maximal GHRH stimulation indicates mediation by a non-GHRH pathway. However, the discordant decrease in TSH responsiveness to TRH argues against a reduction in hypothalamic SRIH secretion as a mechanism for the action of insulin.
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PMID:Discordant effects of insulin-hypoglycemia on growth hormone (GH)-releasing hormone-stimulated GH and thyrotropin (TSH)-releasing hormone-stimulated TSH secretion. 312 17

We studied endocrine functions of the hypothalamus, pituitary, thyroid, gonad, adrenal and pancreas in 26 patients with myotonic dystrophy. The following findings were obtained: (1) Hyporesponsivenesses of HGH to insulin, arginine and L-dopa test were observed in 25%, 45% and 54.5% of patients, respectively. To the administration of sulpiride and TRH, hypo- or hyperresponses of plasma PRL were observed in 4 or 2 patients, respectively. (2) Depressed plasma levels of testosterone were observed in 4 patients and those of estradiol were observed in 3 patients. Among these 7 patients, five were hypergonadotropic and the remaining two were hypogonadotropic. From the data of plasma cortisol and urinary 17-OHCS, the adrenal functions in patients with myotonic dystrophy were considered to be normal. The renin-angiotensin-aldosterone systems in these patients were considered to be grossly normal. (3) Basal levels of T3, T4 and free T4 were within the normal ranges, but 6 of 19 patients showed low levels of 131I-uptake and 11 of 24 patients showed reduced BMR values. (4) The basal level of plasma insulin was elevated in 5 patients. Insulin responses to oral glucose were exaggerated and delayed in 21 of 26 patients. From these results and the statistical evaluation of each laboratory and clinical data, we concluded that 1) the degrees of disturbances of endocrine functions are at random in each patient. 2) The measures of intellectual function obtained by WAIS were directly correlated with basal levels of TSH, but inversely with basal levels of somatostatin. No specific correlation was found between endocrinological disturbances and neurological severities. 3) Impairment of some endocrine functions, such as the gonadal, thyroid and somatotroph functions, was closely correlated with age and the duration of disease.
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PMID:Endocrinological abnormalities in myotonic dystrophy: consecutive studies of eight tolerance tests in 26 patients. 344 27

In previous investigations we observed an increase of growth hormone (HGH) in the blood serum of patients suffering from various clinical forms of psoriasis. The skin lesions disappeared in about 70% when treated systemically with somatostatin and/or bromocriptine, which are inhibitors of HGH secretion. These findings suggested a post mortem investigation of the pituitary glands of 10 patients who had suffered from psoriasis or psoriatic arthritis. Using histochemical and immunochemical methods, we investigated the distribution of cells producing HGH, PRL, LH or FSH. In all 10 pituitary glands we found hyperplasia of the HGH cells, whereas cells producing LH, TSH, FSH and PRL had a normal distribution. The pituitary glands of controls showed no accumulation or hyperplasia of HGH cells.
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PMID:[Hyperplasia of growth hormone-producing cells in the hypophysis in psoriasis. Study of 10 patients]. 353 Oct 93


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